Potassium Hydroxide → tert-Butyl 4-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-4-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2088881Notes

Reaction equation

HRID 2088881 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[N:8]=[C:9]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[NH:10][CH:11]=2)[CH2:3][CH2:2]1.[OH-].[K+].Br[CH2:28][CH2:29][O:30][CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][O:32]1>CS(C)=O>[O:32]1[CH2:33][CH2:34][CH2:35][CH2:36][CH:31]1[O:30][CH2:29][CH2:28][N:10]1[CH:11]=[C:7]([CH:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)[N:8]=[C:9]1[CH:12]1[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 178451797HCID 178451797, compound

Product 1

HCID 67954713tert-Butyl 4-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-4-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-2-yl)piperidine-1-carboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
45 °C

Procedure

Combine tert-butyl 4-(4-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-2-yl)piperidine-1-carboxylate (5.84 g, 17.40 mmol) and potassium hydroxide (5.91 g, 6.0 eq) (freshly powdered) in dimethyl sulfoxide (30 mL). Heat the reaction mixture to 45° C. under nitrogen. After 15 minutes, add 2-(2-bromoethoxy)tetrahydro-2H-pyran (2.90 mL, 1.1 eq). Continue to heat the reaction overnight. Add water and extract with ethyl acetate. Wash the organics with saturated aqueous sodium chloride. Dry the organics over anhydrous magnesium sulfate, filter, and concentrate in vacuo. Purify by silica gel chromatography, eluting with hexanes to 50% ethyl acetate in hexanes to ethyl acetate to 10% methanol in ethyl acetate, to give the title compound as a thick yellow oil (6.94 g, 86%). MS (ES) m/z=464 [M]+.

Workup

  1. temperatureContinue to heat
  2. customthe reaction overnight
  3. extractionAdd water and extract with ethyl acetate
  4. washWash the organics with saturated aqueous sodium chloride
  5. dry with materialDry the organics over anhydrous magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify by silica gel chromatography
  9. washeluting with hexanes to 50% ethyl acetate in hexanes to ethyl acetate to 10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-b1a9b76a41274b5f9e7a87d39beff2c2
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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